Keratinocyte growth factor (KGF) is a recently identified member of the heparin binding growth factor family with activity primarily for epithelial cells. Analysis of the genomic structure of KGF has revealed that it has three exons as do other family members. An unexpected finding, however, is that human genomic DNA contains approximately 16 copies of sequences homologous to exons two and three of KGF. Further analysis of these copies reveals that they are about 97% identical to KGF and have an open reading frame with an initiation codon at the 5' end of exon two. Chromosomal localization by somatic cell hybrid analysis has localized KGF to chromosome 15 while also revealing that the KGF copies are on other chromosomes. Analysis of the evolutionary origin of the partial copies by calculations using a molecular clock model and Southern blot analysis reveals the recent origin of the copies in only the great apes. In order to determine if the KGF-like sequences have a physiologic role, patterns of RNA expression were determined and cDNA's isolated. These cDNA's have been expressed both in vitro and in COS cells.